(1) Field of the Invention
The present invention relates to a process for the preparation of 2-fluoro-9-beta-D-arabinofuranosyl adenine (VII) which is useful in the preparation of 2-Fluoro-Ara-AMP (the phosphate of (III), a cytotoxic agent. The compound (VII) is also known as 9-beta-D-arabinofuranosyl-2-fluoroadenine or 2-F-Ara-A.
(2) Prior Art
Example 4A of U.S. Pat. No. 4,188,378 to Montgomery shows the preparation of 2-fluoro-9-beta-D-arabinofuranosyl adenine (VII) from 2-fluoro-9-(2,3,5-tribenzyl-beta-D-arabinofuranosyl)adenine )VI) using sodium in liquid ammonia with a 34% yield. The most efficient procedure disclosed in this patent is the use of boron trichloride in methylene chloride in Example 4B which produces a 91% yield, but which is difficult and expensive to perform on a large scale since the reaction is performed at -80.degree. C. using liquid nitrogen or dry ice acetone. The reference describes catalytic hydrogenolysis of (VI) in the presence of palladium or palladized charcoal to remove the benzyl group. It suggests that partial defluorination results from this reaction.
J. Org. Chem. 1977, 42, 2309, describes hydrogen transfer from an organic compound to chlorobenzene. Under the reaction conditions employed, fluorobenzene did not react.